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Nobiletin: Targeting the Circadian Network to Promote Bioenergetics and Healthy Aging

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Abstract

The circadian clock is the biological mastermind governing orderly execution of bodily processes throughout the day. In recent years, an emerging topic of broad interest is clock-modulatory agents, including small molecules both of synthetic and natural origins, and their potential applications in disease models. Nobiletin is a naturally occurring flavonoid with the greatest abundance found in citrus peels. Extensive research has shown that Nobiletin is endowed with a wide range of biological activities, yet its mechanism of action remains unclear. We recently found through unbiased chemical screening that Nobiletin impinges on the clock machinery to activate temporal control of downstream processes within the cell and throughout the body. Using animal models of diseases and aging, we and others illustrate potent beneficial effects of Nobiletin on cellular energetics in both periphery and brain to promote healthy aging. Given its excellent safety profile, Nobiletin may represent a promising candidate molecule for development of nutraceutical and chronotherapeutic agents against chronic and age-related neurodegenerative diseases.

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Abbreviations

AD:

Alzheimer’s Disease

CI:

Complex I

CIII:

Complex III

CIV:

Complex IV

CL:

cardiolipin

SC:

supercomplex

NOB:

Nobiletin

TRF:

time-restricted feeding

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Funding

The following authors wish to acknowledge financial support of their laboratories: S.-H. Y. – The Welch Foundation (grant AU-1971-20180324), NIH/NIGMS (grant R01GM114424) and NIH/NIA (grant R03AG063286); W. D. – NIH/NIGMS (grant R01GM115969) and John S. Dunn Research Foundation Grant; Z. C. – The Welch Foundation (grant AU-1731-20190330) and NIH/NIA (grants R01AG045828, RF1AG061901, R56AG063746, and R01AG065984).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, The University of Texas Health Science Center at Houston, 6431 Fannin St., 77030, Houston, TX, USA

    E. Mileykovskaya, S.-H. Yoo, W. Dowhan & Z. Chen

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  1. E. Mileykovskaya
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  2. S.-H. Yoo
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  3. W. Dowhan
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  4. Z. Chen
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Correspondence to E. Mileykovskaya or Z. Chen.

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The authors declare no conflict of interest in financial or any other sphere. This article does not contain any studies with human participants or animals performed by any of the authors.

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Mileykovskaya, E., Yoo, SH., Dowhan, W. et al. Nobiletin: Targeting the Circadian Network to Promote Bioenergetics and Healthy Aging. Biochemistry Moscow 85, 1554–1559 (2020). https://doi.org/10.1134/S000629792012007X

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